Tuberculosis (TB) is a chronic specific granulomatous disease and a major cause of death in developing countries. The clinical presentation of TB lesions of the oral cavity varies widely and can manifest as ulcerations, diffuse inflammatory lesions, granulomas and fissures. Oral lesions generally appear secondary to primary TB infection elsewhere, although primary infection of the oral mucosa by Mycobacterium tuberculosis has also been described. We hereby report a case of primary TB of the gingiva manifesting as gingival enlargement. Diagnosis was based on histopathological examination, complete blood count, X-ray chest and immunological investigations with detection of antibodies against M. tuberculosis. Anti-tuberculous therapy was carried out for over 6 months and was followed by surgical excision of the residual enlargement under local anesthesia. After 1-year follow-up, there was no recurrence of the disease. This case report emphasizes the need for dentists to include TB in the differential diagnosis of various types of gingival enlargements.

Tuberculosis (TB) is a chronic granulomatous infectious disease caused by Mycobacterium tuberculosis; it can affect any part of the body including the oral cavity. Extrapulmonary TBis rare, occurring only in 10-15% of all cases. [1] The average annual risk of TB infection is highest in sub-Saharan Africa (1.5-2.5%) and Asia (1.0-2.0%). [2] In comparison, the average annual risk in developed countries like Netherlands was estimated to be 0.012%. [3] TBshows a high incidence of coexistence with various immunocompromised conditions. In sub-Saharan Africa, about 80% of subjects with TB are coinfected with HIV, and it is estimated that in South Africa 30% of HIV-seropositive subjects have active TB. [4]

Tuberculous lesions of the oral cavity are so rare that this manifestation of disease is often overlooked. [5],[6] Oral TBcan be primary or secondary. Primary oral tuberculous lesions are extremely rare and generally occur in young adults with associated caseation of the dependent lymph nodes; the lesion itself remains painless in most cases. [7],[8] Oral TB accounts for up to 1.33% of HIV-associated opportunistic infections. [9] In contrast, secondary oral TBis seen in about 0.05- 1.5% of reported cases and usually occurs in older adults. [10],[11] In oral TB, the most commonly affected site is the tongue; other sites include the lip, cheek, soft palate, uvula, gingiva and alveolar mucosa. [12] The lesions are seen as superficial ulcers, [13],[14] patches, [6] indurated soft tissue lesions [15] oreven lesions within the jaw in the form of tuberculous osteomyelitis. [16]

The mode of spread of tuberculous infections isthrough airborne particles, when an infectious patient coughs, sneezes, talks or sings. [17] Because TB is highly infectious and its airborne transmission is difficult to control, the CDC has issued specific guidelines to help protect health care workers when treating patients. [18] These guidelines state that the elective dental treatment should be postponed for patients who are suspected of having infectious TB or who have been identified as active TB cases. [19]

If emergency treatment is to be performed on a patient suspected of having infectious TB, the precautions taken include scheduling the patient at the end of the day, as the last patient treated and the use of appropriate barrier precautions. Staff assisting in the dental treatment must also be aware of their immune status for the relevant infectious disease of the patient. [19] The use of rubber dam andhigh-volume evacuation is recommended to reduce dental care provider and dental staff exposure to potentially infected aerosols. All team members present in the treatment room must wear a HEPA or NIOSH N 95 mask. [20]

To prevent cross-infection, schedule the patient at the end of the day, as the last patient treated. All team members present in the treatment room must wear a HEPA or NIOSH N 95 mask. High-volume evacuation and dental dam isolation should be used to reduce aerosols and minimalize use of ultrasonic scalers and high-speed handpiece. The operatory air should be vented to the outside (i.e., not recirculated). [21] For infection control, elective dental treatment should be differed until sputum culture and all the tests like enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) are negative. [22]

We are hereby reporting a case of primary tuberculous gingival enlargement presenting as an initial sign of TB, with no regional lymph node involvement and no evidence of systemic TB.

Case report

A 23-year-old girl reported to the Department of Periodontics and Oral Implantology, Government Dental College and Hospital, Srinagar, Kashmir, with progressive, non-painful swelling of the gingiva on the labial aspect of the upper and lower anterior teeth with 6 months' duration. There was a history of evening rise in temperature and weakness over the last 3 months. The patient also had a loss of appetiteover the last 4 months and a weight loss of about 4.5 kg during the last 8 months.

Medical history

There was no systemic problems, no cough with expectoration, no history of dental trauma or surgery in the affected area.

Extraoral examination

The cervical lymph nodes were not palpable.

Intraoral examination

The intraoral examination showed diffuse enlargement of the upper and lower gingiva on the labial surface of anterior [Figure 1]. On palpation, the swelling was slightly tender and firm. The rest of the oral cavity was normal except for the few deep carious teeth. According to Silnessand Lφe, the plaque index score was also good (score: 0.6).

Figure 1: Diffuse enlargement of both the arches and lobulated appearance of the mandibular labial gingiva extending up to the left first molar

Differential diagnosis showed enlargement due to drugs, infection and hematologic malignancy. The possibility of drug-induced enlargement was ruled out based on medical history.

Biochemical tests

The biochemical tests were within normal limits, except for a marginal rise in leukocyte count (13 × 10 9 /L) and an elevated erythrocyte sedimentation rate (ESR) of 56 mm/h (Westergren method), which ruled out leukemia-associated enlargement and raised the possibility of one of the commoner causes of high ESR, TB.

Histopathologic examination

An incisional biopsy was carried out in relation to the gingiva of the mandibular right central incisor. The excised material was fixed in 10% neutral buffered formalin fixative (a 4% solution of formaldehyde) to stop tissue autolysis prior to the sample reaching the pathology lab. Histopathologic examinationwas carried out that revealed clusters of epithelioid cells surrounded by a chronic inflammatory type of infiltrate. There was no evidence of caseating necrosis, but numerous Langerhans-type of giant cells were visible in the clusters of epithelioid cells suggestive of a "hard tubercle" [Figure 2] and [Figure 3]. To eliminate the possibility of localized granulomatous changes superimposed on an area of gingival enlargement, incisional biopsy was repeated in the remaining three quadrants. Histopathology showed similar granulomatous changes in all tissue specimens examined.

Chest radiography (posteroanterior view) revealed no abnormalities [Figure 4]. A computed tomographyscan of the head and neck region was also performedto determinethe status of the underlying maxilla and mandible. The scan did not reveal any bone abnormalities [Figure 5].

A culture of the sputum, obtained by forceful coughing, was negative for M. tuberculosis. Special staining of formalin-fixed, paraffin-embedded tissue specimens for Mycobacteria, i.e., Ziehl - Neelsen and Auramine - Rhodamine stain, was negative.

Immunologic testing

An immunologic test to detect antibodies against Mycobacteriumin the patient's serum (ELISA) was positive. PCR assay was also carried out using six 5-μm sections of paraffin-embedded tissue to identify specific sequences of M. tuberculosis complex, with adequate controls. The DNA was used as an amplifying target for the sequence IS-6110, which is specific for M. tuberculosis. Positive PCR results confirmed the presence of M. tuberculosis in the tissue samples.

Final diagnosis

In view of these findings, a final diagnosis of primary tuberculous gingival enlargement was made.

Treatment

In consultation with the patients' physicians, anti-tubercular therapy was initiated. During this period, the patient was instructed not to undergo any ultrasonic scaling and polishing or surgical procedure within the oral cavity and was warned about the chance of transmitting the disease to others via aerosol and salivary contamination. After completion of a 6-month regimen of basic periodontal therapy, which included scaling and root planing, oral hygiene instructions were instituted under CDC-issued guidelines. This resulted in significant regression of the enlarged gingivae in both the arches. Gingivectomy and gingivoplasty wereperformed to shape and contour the residual enlargement under universal aseptic conditions [21][Figure 6]. No recurrence of lesion occurred during 1-year follow-up [Figure 7].

TB remains the leading cause of death worldwide from a single infectious organism. Approximately 32% of the world's population is infected with TB and an estimated 2 million people die annually from this treatable disease. [23]

In the Indian population, the average prevalence of all forms of TB has been reported to be 5.05 per 1000. [24] Although oral TB has been well documented, tuberculous lesions of the upperaerodigestive tract are rare. Therefore, intraoral TB is generally missed in the differential diagnosis of this entity, and there are many patients in whom the correct diagnosis and therapy are delayed or missed entirely.

The mechanism of primary inoculation of tuberculous bacilli into the oral mucous membrane is not clearly understood, althoughingestion of milk contaminated with M, bovis by children and adolescents has been presumed to be one probable factor. [25] One reason for the rare occurrence of TB of the gingiva may be that the intact squamous epithelium of the oral cavity resists direct penetration of bacilli. [13] This resistance has been attributed to the thickness of the oral epithelium, the cleansing action of saliva, local pH and antibodies in saliva. [1] Even if the onset of infection is by hematogenous spread, injured or inflamed tissue tends to localize blood-borne bacteria. However, the mode of entry of the microorganism may be through a break in the mucous membrane caused by local trauma. [26] Where the infection involves the bone, the mode of entry is thought to be through an extraction socket. However, there is general consensus that secondary TBspreads by a hematogenous route. [27]

There is a high incidence of TBin immunocompromised patients as well, especially in HIV patients such that HIV and TB coinfection constitutes a serious public health problem. It is estimated that one-third of the persons living with HIV infection are coinfected with TB. This coinfection is so clinically relevant that current guidelines recommend that HIV testing be performed in every individual diagnosed with TB. [28]

The case report presented here is one of the first few cases of primary tuberculous gingival enlargement in the literature. The oral lesion in this case is diffuse gingival enlargement instead of the usual manifestation as an ulcer [29] or localized granular mass. [30] There was no neck node involvement secondary to the primary involvement. [31] In the present case, the tuberculin test was positive, indicating previous exposure to the TB bacilli. An immunological test was also carried out for the detection of antibodies to M. tuberculosis, and it was found to be positive. However, anti-tubercular antibodies may also occur in those who have been exposed to the organism before; thus, this test is not considered to confirm a diagnosis of active disease and hence histopathological examination was carried out. Histopathologic examination and identification of the bacilli using special stains lead to the presumption of a diagnosis of TB.

There is always a need for rapid and sensitive detection of M. tuberculosis in tissue specimens, as culture techniques lack sensitivity, present technical difficulties and require a wait of 4-6 weeks for results. [32] In addition, sputum-based tests are unsuitable forthediagnosis of extra-pulmonary, smear-negative and pediatric TB. From an economic perspective, importedmolecular or liquid culture tests are too expensive, leaving serological tests as the main alternative. DNA amplification was hence carried out using PCR technology as it is highly useful for detecting M. tuberculosis in formalin-fixed, paraffin-embedded tissue samples. [33] Tuberculous granulomas that are negative for M. tuberculosis using culture techniques or special stains mayturn out to be positive for its DNA by the amplification process.

In the present case, PCR was used to detect M. tuberculosis DNA as it is known to be highly sensitive (94%) and specific (98%) compared withtissue culture techniques. [34] It is known to detect DNA even when only few genomes are present. [31] The diagnosis of tuberculous gingival enlargement based on the histopathologic examination was thus confirmed by PCR.

Infection control guidelines for tuberculosis cases

Surgical masks do not prevent inhalation of M. tuberculosis droplet nuclei; therefore, standard precautions are not sufficient to prevent transmission of this organism. Recommendations for expanded precautions to prevent transmission of M. tuberculosis and other organisms that can be spread by airborne, droplet or contact routes have been detailed.

TB transmission is controlled through a hierarchy of measures, including administrative controls, environmental controls and personal respiratory protection. The main administrative goals of a TB infection-control program are early detection of a person with active TB disease and prompt isolation from susceptible persons to reduce the risk of transmission. Dental health care personnel (DHCP) should be trained to recognize signs and symptoms of TB to help with prompt detection.

Elective dental treatment should be deferred until a physician confirms that a patient does not have infectious TB or, if the patient is diagnosed with active TB disease, until confirmed that the patient is no longer infectious.

If urgent dental care is provided for a patient who has, or is suspected of having, active TB disease, the care should be provided in a hospital facility that provides airborne infection isolation (i.e., using such engineering controls as TB isolation rooms, negatively pressured relative to the corridors, with air either exhausted to the outside or HEPA-filtered if recirculation is necessary). Standard surgical face masks do not protect against TB transmission; DHCP should use respiratory protection (e.g. fit-tested, disposable N-95 respirators).

Any DHCP with a persistent cough (i.e., lasting >3 weeks), especially in the presence of other signs or symptoms compatible with active TB (e.g. weight loss, night sweats, fatigue, bloody sputum, anorexia or fever), should be evaluatedpromptly. The DHCP should not return to the workplace until a diagnosis of TB has been excluded or the DHCP is on therapy and a physician has determined that the DHCP is non-infectious.

Evaluate the patient away from other patients and DHCP. When not being evaluated, the patient should wear a surgical mask or be instructed to cover the mouth and nose when coughing or sneezing.

To conclude and summarize it all, it was found that tuberculous infection of the gingiva is a relatively rare entity; oral lesions generally manifest secondary to pulmonary TB. Hence, to characterize oral lesions as primary TB, a thorough examination to rule out other primary sites should be attempted. With the recent increase in the incidence of TB, clinicians need to be aware of this possibility and should consider TBin the differential diagnosis of gingival enlargement, which can be helpful in the early detection and treatment of this disease.